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Design, synthesis and biological evaluation of novel steroidal spiro-oxindoles as potent antiproliferative agents
- Source :
- The Journal of steroid biochemistry and molecular biology. 141
- Publication Year :
- 2013
-
Abstract
- Two series of novel steroidal spiro-pyrrolidinyl oxindoles 3a-t and 6a-c were designed and synthesized from dehydroepiandrosterone using the 1,3-dipolar cycloaddition as the key step and further evaluated for their antiproliferative activities for four human cancer cell lines (MGC-803, EC109, SMMC-7721 and MCF-7). This protocol achieved the formation of two CC bonds, one CN bond and the creation of one new five-membered pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spiro-pyrrolidinyl oxindoles possessed moderate to good antiproliferative activities against the tested cell lines and some of them were more potent than 5-Fu. Particularly, compound 3g showed good antiproliferative activity against SMMC-7721 (IC50=0.71μM). Steroid dimer 6b showed improved antiproliferative activities against SMMC-7721 and MCF-7 with the IC50 values of 4.30 and 2.06μM, respectively. Flow cytometry analysis demonstrated that compound 3n caused the cellular early apoptosis and cell cycle arrest at G2/M phase in a concentration- and time-dependent manner. [Corrected]
- Subjects :
- Cell cycle checkpoint
Indoles
Pyrrolidines
Stereochemistry
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Dimer
Clinical Biochemistry
Antineoplastic Agents
Apoptosis
Biochemistry
Pyrrolidine
Steroid
chemistry.chemical_compound
Endocrinology
Cell Line, Tumor
medicine
Humans
Spiro Compounds
Molecular Biology
IC50
Cell Proliferation
Cycloaddition Reaction
Cell growth
Cell Biology
Cell Cycle Checkpoints
Ketosteroids
Cycloaddition
chemistry
Drug Design
1,3-Dipolar cycloaddition
Molecular Medicine
Drug Screening Assays, Antitumor
Subjects
Details
- ISSN :
- 18791220
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Accession number :
- edsair.doi.dedup.....00b009cb4a0feba980e1054125ad195a